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H5N1 Qinghai Strain in Liaoning China

Recombinomics Commentary
April 6, 2006

The recent report from the Ministry of Health in China provides additional detail on human isolates in Turkey, as well as the outbreak in Liaoning Province in China.  The phylogenetic tree on slide seven provides the additional information.  The tree confirms that the Fujian strain of H5N1 is widespread in China.  The clade that includes Duck/Fujian/1734/05 also includes the six human isolates (Anhui/1/2005, Anhui/2/2005, Sichuan/1/2006, Fujian/1/2005, Jiangxi/1/2005) as well as another bird isolate, CK/Hunan/21/2005.  The HA of all of these isolates are more than 99% homologous to the Fujian Duck isolate, which is also related to recent isolates in Laos and Malaysia.

However, the isolate from Liaoning, CK/Liaoning/23/2005 is listed in the Qinghai clade.  These data indicate that there are two distinct strains of H5N1 circulating in China.  In addition to the Fujian strain, which was more easily contained with the bird vaccine used in China, than the Qingahi strain, which was difficult to contain.  Although the Liaoning isolate is in the Qinghai clade, it was distinct from the isolates from Qinghai Lake as well as the Qinghai isolates in Turkey.

The phylogenetic tree provides additional information that is not publicly available in the deposited sequences.  Weybridge has deposited the HA sequence from the initial turkey isolate from October, 2005, turkey/Turkey/1/2005.  However, the more recent isolates, including the human isolates form 2006 have not been made public.  The tree indicates the two human isolates, Turkey/12/2006 and Turkey/15/2006, are more closely related to a chicken isolate from 2005, chicken/Turkey/5/2005.  Moreover, the tree suggests that the isolates from the index case and his sister are identical.  Since the report also indicates that the isolate from the index case has S227N, it seems that the tree contradicts media reports indicating that the sister's isolate did not contain S227N.  This initial report may be related to how the sisters isolate was cultured.  Culturing in chicken eggs would select against S227N, but growth on mammalian cells like MDCK would increase the likelihood of detection of changes in the receptor binding domain that would increase affinity to mammalian receptors.

Although the phylogenetic tree released by the Ministry of Health in China is useful, the full release of sequences held by Weybridge would be useful.  By now all eight genes from the isolates from Turkey would have been sequenced, as would dozens of additional sequences from Europe.  H5N1 continues to evolve via recombination, and a complete and up to date database is important for predicting additional changes.  Although China's ministry of health acknowledges both recombination and reassortment as mechanisms of H5N1 acquisition of human sequences, the WHO consultants actively ignore recombination, which is the main driver of rapid genetic changes in influenza in general, and H5N1 in particular.

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